Effect of human recombinant erythropoietin on anaemia and dialysis efficiency in patients undergoing continuous ambulatory peritoneal dialysis

The effect of long-term treatment with human recombinant erythropoietin (rHuEPO) has been studied in nine end-stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD). RHuEPO was administered subcutaneously twice weekly in rising doses starting with 50 Ukg-1 body weight. After 3 months of rHuEPO haemoglobin increased from 77.7 +/- 3.2 to 112.7 +/- 5.6 g l-1 (P less than 0.03), haematocrit rose from 22.8 +/- 1.2 to 30.3 +/- 1.7% (P less than 0.01). A consistent decrease in ferritin concentration was observed during this time (P less than 0.05). After 12 months of rHuEPO treatment and increased oral iron supplementation the rises of haemoglobin and haematocrit remained stable without other significant haematological changes. The rHuEPO-induced rise in haematocrit was associated with an increased peritoneal ultrafiltration (UF) without change in diuresis and body weight. UF improved from 128 +/- 28 ml 4 h-1 dwell time to 273 +/- 45 ml 4 h-1 (P less than 0.03) within 3 months of rHuEPO treatment, and remained stable during the following study period (month 12: 253 +/- 43 ml 4 h-1, P less than 0.05). The rise in UF resulted in improved peritoneal clearances of creatinine, urea, potassium, and phosphate (P less than 0.05, month 3). No change was observed in serum urea, creatinine, calcium, and potassium. Serum phosphate increased throughout the first 6 months of rHuEPO (P less than 0.05). No severe adverse effects of rHuEPO treatment could be observed. The present results demonstrate that long-term subcutaneous administration of rHuEPO is effective in correcting renal anaemia in CAPD patients and may improve dialysis efficiency by increased peritoneal ultrafiltration.     

Contribution of lymphatic absorption to loss of ultrafiltration and solute clearances in continuous ambulatory peritoneal dialysis.

The contribution of peritoneal cavity lymphatic absorption to ultrafiltration kinetics and solute clearances in continuous ambulatory peritoneal dialysis was evaluated in patients with normal (group 1) and high (group 2) peritoneal permeability X area during 4-h exchanges using 2 liters 2.5% dextrose dialysis solution with 30 g added albumin. Cumulative lymphatic drainage in all continuous ambulatory peritoneal dialysis (CAPD) patients averaged 358 +/- 47 ml per 4-h exchange and reduced cumulative net transcapillary ultrafiltration at the end of the exchange by 58 +/- 7.2%. The peak ultrafiltration volume was observed before osmotic equilibrium between serum and dialysate was reached and occurred when the net transcapillary ultrafiltration rate had decreased to equal the lymphatic absorption rate. Thereafter the lymphatic absorption rate exceeded the net transcapillary ultrafiltration rate, and intraperitoneal volume decreased. Extrapolated to 4 X 2 liters, 2.5% dextrose, 6-h exchanges per d, lymphatic drainage reduced potential daily net ultrafiltration by 83.2 +/- 10.2%, daily urea clearance by 16.9 +/- 1.9%, and daily creatinine clearance by 16.5 +/- 1.9%. Although lymphatic absorption did not differ between the two groups, lymphatic drainage caused a proportionately greater reduction in net ultrafiltration in group 2 (P less than 0.025), because these patients had more rapid dialysate glucose absorption (P less than 0.05) and less cumulative transcapillary ultrafiltration (P less than 0.01). These findings indicate that cumulative lymphatic drainage significantly reduces net ultrafiltration and solute clearances in CAPD and that ultrafiltration failure in CAPD occurs when daily lymphatic absorption equals or exceeds daily transcapillary ultrafiltration. Reduction of lymphatic absorption may provide a means for future improvement in the efficiency of CAPD.     

Beta-2 microglobulin in patients on peritoneal dialysis and hemodialysis

Serum beta 2 microglobulin (beta 2 mu) levels were determined in 62 patients on chronic dialysis, divided according to the type of dialysis--cuprophane hemodialysis, chronic ambulatory peritoneal dialysis (CAPD), or CAPD started after 76 +/- 47 months on cuprophane hemodialysis--and to residual urine output greater than 400 mL/day or less than 10 mL/day. In addition, for patients on CAPD, peritoneal excretion, peritoneal clearance, and urinary excretion of the protein were determined. In anuric patients serum beta 2 mu levels were significantly higher in HD than in CAPD. In patients with residual urine output, serum concentrations of the microprotein were similar in HD and in CAPD. Significant differences were observed in beta 2 mu serum levels and peritoneal clearances in patients switched to CAPD from hemodialysis as compared to those starting with CAPD. Peritoneal clearances of the microprotein was slightly and non-significantly greater in patients with urine output than in anuric patients.     

Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD.

Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C-PTH and MM-PTH serum levels by peritoneal losses of these fragments.     

Serum BNP concentration and left ventricular mass in CAPD and automated peritoneal dialysis patients.

OBJECTIVE: To compare ultrafiltration under continuous ambulatory peritoneal dialysis (CAPD) and automated PD (APD), disclosing potential effects on serum B-type natriuretic peptide (BNP) levels and echocardiographic findings. PATIENTS AND METHODS: This cross-sectional clinical study included 32 patients on CAPD and 30 patients on APD without clinical evidence of heart failure or hemodynamically significant valvular heart disease. Peritoneal equilibration tests, BNP levels, and echocardiographic measurements were performed in each subject. BNP measurements were also performed in 24 healthy control subjects. RESULTS: Patients on APD had lower ultrafiltration and higher values of BNP and left ventricular mass index (LVMI) compared with patients on CAPD (respectively: 775 +/- 160 vs 850 +/- 265 mL, p = 0.01; 253.23 +/- 81.64 vs 109.42 +/- 25.63 pg/mL, p = 0.001; 185.12 +/- 63.50 vs 129.30 +/- 40.95 g/m(2), p = 0.001). This occurred despite higher mean dialysate glucose concentrations and far more extensive use of icodextrin in the APD group. CONCLUSION: Treatment with APD is associated with higher plasma BNP levels and LVMI compared to CAPD. This may be the result of chronic fluid retention caused by lower ultrafiltration in APD patients.     

Effects of peritoneal resting on peritoneal fluid transport kinetics.

BACKGROUND: Peritoneal resting has been used to restore peritoneal ultrafiltration capacity in peritoneal dialysis patients. Therefore, in the present study, we made a detailed investigation on the effects of peritoneal resting on peritoneal fluid transport characteristics in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: A temporary transfer to daytime ambulatory peritoneal dialysis with a nocturnal "empty belly" was applied to let the peritoneal membrane rest overnight in patients with poor ultrafiltration capacity. All included patients were asked to record appropriately their dialysis exchanges for the assessment of peritoneal fluid transport characteristics, which were evaluated before and after peritoneal resting. RESULTS: Seven CAPD patients were included in the present study. There was a significant improvement in peritoneal ultrafiltration capacity as assessed by ultrafiltration volume per gram of glucose load. Patients' daily glucose exposure and dialysate-to-plasma ratio of creatinine were significantly decreased after peritoneal resting. The peritoneal fluid absorption rate was also significantly decreased after peritoneal resting: 1.011 +/- 0.4484 versus 0.625 +/- 0.3833 mL/minute. CONCLUSION: The present study suggests that peritoneal resting can improve CAPD patients' ultrafiltration capacity and decrease the use of hypertonic dialysis solution. The improved ultrafiltration capacity by peritoneal resting was due to decreased membrane solute transport rate and decreased peritoneal fluid absorption rate.     

Peritoneal functional parameters after five years on continuous ambulatory peritoneal dialysis (CAPD): the effect of late peritonitis

Functional stability of the peritoneum is essential for patients on long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Sixteen patients on CAPD treatment for at least 4 years were studied. Their mean age was 47 +/- 15 years, 5 were males, and none were diabetic. Residual creatinine clearance at the beginning was 2.1 +/- 2.6 mL/min. Once yearly since starting CAPD, we have evaluated their peritoneal ultrafiltration (UF) and diffusion capacities by calculating the peritoneal mass transfer coefficient (MTC, mL/min) for urea and creatinine. Patients were categorized so that we could distinguish the effect of peritonitis, betablockers, and hypertension. For all patients the average initial and final MTCs and UF values were not different. Early episodes of peritonitis (those occurring less than 36 months after starting CAPD) did not influence long-term function. However, late peritonitis (occurring greater than 36 months since initiation) induced a decrease in urea-MTC (22.3 +/- 6 to 15.8 +/- 3.9, p less than 0.05), creatinine-MTC (9.4 +/- 3.1 to 7.4 +/- 2.5, p less than 0.05), and a corresponding increase in UF (1.25 +/- 0.4 to 1.4 +/- 0.3, mL/min, p less than 0.05). Age, sex, betablockers and hypertension did not influence the peritoneal parameters followed. After 5 years on CAPD, functional stability of the peritoneum is evident, except for patients who suffer late episodes of peritonitis. We speculate that the peritoneum in patients who have been on long-term CAPD are more susceptible to injuries, such as peritonitis, and that this results in functional deterioration.     

Peritoneal accumulation of AGE and peritoneal membrane permeability.

BACKGROUND: In continuous ambulatory peritoneal dialysis (CAPD), the peritoneal membrane is continuously exposed to high-glucose-containing dialysis solutions. Abnormally high glucose concentration in the peritoneal cavity may enhance advanced glycosylation end-product (AGE) formation and accumulation in the peritoneum. Increased AGE accumulation in the peritoneum, decreased ultrafiltration volume, and increased peritoneal permeability in long-term dialysis patients have been reported. AIM: The purpose of the study was to evaluate the relation between peritoneal membrane permeability and peritoneal accumulation of AGE. METHODS: Peritoneal membrane permeability was evaluated by peritoneal equilibration test (PET) using dialysis solutions containing 4.25% glucose. Serum, dialysate, and peritoneal tissue levels of AGE were measured by ELISA method using polyclonal anti-AGE antibody. Peritoneal biopsy was performed during peritoneal catheter insertion [new group (group N), n = 18] and removal [long-term group (group LT), n = 10]. Peritoneal catheters were removed due to exit-site infection not extended into the internal cuff (n = 6) and ultrafiltration failure (n = 4) after 51.6+/-31.5 months (13 - 101 months) of dialysis. PET data obtained within 3 months after the initiation of CAPD or before catheter removal were included in this study. Ten patients in group N and 4 patients in group LT were diabetic. Patients in group LT were significantly younger (46.5+/-11.1 years vs 57.5+/-1.3 years) and experienced more episodes of peritonitis (3.5+/-2.1 vs 0.2+/-0.7) than group N. RESULTS: Peritoneal tissue AGE level in group LT was significantly higher than in group N, in both nondiabetic (0.187+/-0.108 U/mg vs 0.093+/-0.08 U/mg of hydroxyproline, p < 0.03) and diabetic patients (0.384+/-0.035 U/mg vs 0.152+/-0.082 U/mg of hydroxyproline, p < 0.03), while serum and dialysate levels did not differ between the groups in both nondiabetic and diabetic patients. Drain volume (2600+/-237 mL vs 2766+/-222 mL, p = 0.07) and D4/D0 glucose (0.229+/-0.066 vs 0.298+/-0.081, p < 0.009) were lower, and D4/P4 creatinine (0.807+/-0.100 vs 0.653+/-0.144, p< 0.0001) and D1/P1 sodium (0.886+/-0.040 vs 0.822+/-0.032, p < 0.0003) were significantly higher in group LT than in group N. On linear regression analysis, AGE level in the peritoneum was directly correlated with duration of CAPD (r = 0.476, p = 0.012), number of peritonitis episodes (r = 0.433, p = 0.0215), D4/P4 creatinine (r = 0.546, p < 0.027), and D1/P1 sodium (r = 0.422, p = 0.0254), and inversely correlated with drain volume (r = 0.432, p = 0.022) and D4/D0 glucose (r = 0.552, p < 0.0023). AGE level in the peritoneal tissue and dialysate were significantly higher in diabetics than in nondiabetics in group LT, while these differences were not found in group N. Serum AGE level did not differ between nondiabetics and diabetics in either group N or group LT. Drain volume and D4/D0 glucose were lower and D4/P4 creatinine and D1/P1 sodium higher in diabetics than in nondiabetics in both groups. CONCLUSION: Peritoneal accumulation of AGE increased with time on CAPD and number of peritonitis episodes, and was directly related with peritoneal permeability. Peritoneal AGE accumulation and peritoneal permeability in diabetic patients were higher than in nondiabetic patients from the beginning of CAPD.     

Amino-acid-based continuous ambulatory peritoneal dialysis (CAPD) fluid over twelve weeks: effects on carbohydrate and lipid metabolism

Aspects of lipid and carbohydrate metabolism were studied in 8 patients established on continuous ambulatory peritoneal dialysis (CAPD) with plasma albumin less than 35 g/L, before, during, and after substitution of 1 of the daily glucose exchanges by a commercial 1% amino acid dialysis fluid for 12 weeks. The amount of glucose absorbed from the dialysis fluid was consequently reduced by about 25%, hence total energy intake decreased by about 100 Kcal/day, but peritoneal glucose transfer kinetics were unaffected. Glucose was lost into amino acid dialysate as expected (2 g/day). Excluding 1 patient with a large rise in calorie intake, total and LDL cholesterol fell at 8 and 12 weeks (LDL cholesterol week 0, 5.26 +/- 1.13; week 8, 4.32 +/- 0.74; week 12, 4.30 +/- 1.22; mean +/- SD, p less than 0.01 for both), but returned to baseline 2 weeks after the restoration of glucose fluid (LDL 4.91 +/- 1.22, p less than 0.05 vs. week 12). Apolipoprotein B concentration also fell at 12 weeks (p less than 0.01). No changes were seen in body weight, body fat, arm muscle circumference, fasting plasma glucose, insulin, growth hormone, triglyceride, nonesterified fatty acids, or HDL cholesterol. The response of these biochemical indices to single 8-h glucose and amino acid morning exchanges at 0 and 12 weeks were studied. After 12 week's use of amino acid dialysis fluid, plasma cholesterol and apolipoprotein B were significantly lower throughout the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficient monthly subcutaneous administration of darbepoetin in stable CAPD patients.

BACKGROUND: Although subcutaneous administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients is a widely accepted recommendation, the lowest possible frequency of an efficient dosing regimen remains controversial. Darbepoetin alpha, a new erythropoiesis-stimulating protein with a threefold longer serum half-life compared with rHuEPO, has greater in vivo potency and can be administered less frequently to obtain the same biological response. This study assessed the efficacy of darbepoetin administered once monthly in the treatment of anemia in CAPD patients. PATIENTS AND METHODS: In this single-center, prospective cohort study, 11 stable CAPD patients (5 males, 6 females; mean age 68.8 +/- 14.1 years; mean duration on peritoneal dialysis 31.6 +/- 13 months) maintained average hemoglobin and hematocrit levels of 12.09 +/- 1.29 g/dL and 37.29% +/- 3.58%, respectively, while receiving a mean weekly maintenance dose of epoetin alfa of 129 IU/kg. These same patients were assigned to receive the equivalent weekly darbepoetin dose once monthly for 24 consecutive weeks. Hematological response, iron status (transferrin saturation, serum ferritin levels), C-reactive protein (CRP), and the patients' biochemical profiles were evaluated monthly. RESULTS: During the monthly administration of darbepoetin, mean serum levels of Hb and Hct were 12.17 +/- 1.28 g/dL and 37.1% +/- 1.19% respectively. No statistically significant difference was apparent between the previous and monthly dosing values (12.09 +/- 1.29 vs 12.17 +/- 1.28 g/dL, p = 0.769, and 37.29% +/- 3.58% vs 37.1% +/- 1.19%, p = 0.752). Transferrin saturation levels as well as serum ferritin levels also remained unchanged (30.4% +/- 8.6% vs 30.1% +/- 9.4%, NS, and 556 +/- 212 vs 621 +/- 234 ng/mL, respectively, NS). CONCLUSION: These results indicate that darbepoetin alfa can be effectively given subcutaneously at monthly intervals for the treatment of anemia in stable CAPD patients. However, more studies are needed to validate the long-term efficacy of this monthly subcutaneous administration.     

Erythropoietin in continuous ambulatory peritoneal dialysis: experience with subcutaneous administration.

Experience in the use of subcutaneous erythropoietin (EPO) in 32 continuous ambulatory peritoneal dialysis (CAPD) patients is presented. All patients were treated with oral iron supplements. The total and mean +/- SD durations of EPO treatment were 466 weeks and 14.6 +/- 10.1 weeks respectively. Twenty-two patients started treatment with normal or elevated iron stores; 10 had an initial iron saturation less than 20%. The initial hematocrit was 23.8 +/- 3.7%. Thirteen patients reached a steady-state hematocrit by the end of the study period, when the mean +/- SD hematocrit for all 32 patients was 34.1 +/- 3.6%. All patients responded to EPO. The initial dose of EPO was 147.1 +/- 53.8 U/kg/week. Maintenance dose was 72 +/- 36 U/kg/week.     

The association of peritoneal transport properties with 24-hour blood pressure levels in CAPD patients.

OBJECTIVES: We aimed to investigate the effects of peritoneal transport characteristics on blood pressure (BP) parameters, measured by 24-hour ambulatory blood pressure monitoring (ABPM), and on the development of left ventricular hypertrophy (LVH) in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Cross-sectional and prospective design. SETTING: Tertiary-care center. PATIENTS: 25 CAPD patients (11 male, 14 female; mean age 47 +/- 14 years) were included. Mean time on CAPD was 22.9 +/- 18 months and all patients had been dialyzed for more than 6 months. The patients were divided into high, high-average, low-average, and low transport groups according to peritoneal equilibration test results. MAIN OUTCOME MEASURES: Daytime and nighttime systolic and diastolic BP and left ventricular mass index among the different peritoneal transport groups; changes in BP parameters before and after increase in ultrafiltration. RESULTS: On 24-hour ABPM records, 13 patients (52%) were found to be hypertensive. Both mean systolic and diastolic BP were significantly increased in high-transporter groups compared to low transporters in both daytime and nighttime BP parameters. Left ventricular mass index was higher in high transporters compared to low transporters, without reaching statistical significance: 160 +/- 23 vs 119 +/- 41 g/m2, p > 0.05. Following increase in ultrafiltration, mean systolic (145 +/- 13 vs 128 +/- 5 mmHg, p < 0.001) and diastolic (96 +/- 10 vs 81 +/- 3 mmHg, p < 0.001) BP decreased, and BP levels returned to normotensive levels in 6 (46%) of the 13 hypertensive patients, requiring discontinuation of antihypertensive drugs. CONCLUSION: Improvement in volume status resulted in a decrease in both daytime and nighttime BP. Differences in peritoneal transport properties were associated with the development of hypertension and LVH.     

Peritoneal ultrafiltration and serum icodextrin concentration during dialysis with 7.5% icodextrin solution in Japanese patients.

OBJECTIVES: To assess the efficacy and safety of icodextrin in Japanese patients and to investigate the relationship between net ultrafiltration (UF) during the long dwell and plasma oligosaccharides. DESIGN: Open-labeled clinical trial involving patients on continuous ambulatory peritoneal dialysis (CAPD) receiving icodextrin during the 12-hour long dwell for 6 weeks, preceded by and followed by a 2-week baseline period and a follow-up period during which 1.36% glucose was used for the 8-hour long dwell. SETTING: A prospective, randomized multicenter study done in tertiary medical centers. PATIENTS: 18 stable patients on CAPD for 3 months or longer. MAIN OUTCOMES MEASURES: Net UF (in milliliters), UF rate (in milliliters per hour), plasma oligosaccharides, serum osmolarity (in milliosmoles per liter), peritoneal absorption of icodextrin, and peritoneal clearances of icodextrin, creatinine, and urea were assessed. Adverse events, laboratory findings, and vital signs were also monitored. RESULTS: Long-dwell net UF (544.4 +/- 96.7 mL at day 3, p < 0.001; 309.4 +/- 60.7 mL at week 4, p < 0.001; and 391.7 +/- 61.1 mL at week 6, p < 0.001) and UF rate (48.2 +/- 38.8 mL/ hour at day 3, p < 0.001; 26.9 +/- 22.1 mL/hr at week 4, p < 0.002; and 35.3 +/- 22.9 mL/hr at week 6, p = 0.0002) were significantly greater during the icodextrin period than at baseline (-25.9 +/- 46.0 mL and -2.2 +/- 22.1 mL/hr, respectively). Plasma oligosaccharides reached steady state within 2 weeks, remained stable during the treatment period, and returned to baseline level 2 weeks after discontinuation of icodextrin. Serum osmolarity increased during the use of icodextrin by approximately 5 mOsm/L. No statistically significant relationship was found between plasma oligosaccharides and net UF. Peritoneal absorption of icodextrin (36.3% +/- 5.1% at day 3, 42.2% +/- 5.9% at week 4, and 38.0% +/- 6.3% at week 6) and peritoneal clearance of icodextrin (10.1 mL/minute at day 3, 10.1 mL/min at week 4, and 10.3 mL/min at week 6) showed no major change over time. Serum sodium and serum chloride both decreased by 5 mEq/L with icodextrin but remained within the normal range during the treatment period and returned to baseline levels immediately after discontinuation. No serious adverse events were observed during the study. CONCLUSION: The results of this study do not support the hypothesis that an increased blood oligosaccharide level and the concomitant elevation in serum osmolarity have a negative impact on peritoneal UF. Therefore, the increase in plasma oligosaccharides appears to be too small to be of clinical significance.     

Impact of fill volume on peritoneal clearances and cytokine appearance in peritoneal dialysis.

BACKGROUND: Current adequacy guidelines for peritoneal dialysis encourage the use of large fill volumes for the attainment of small solute clearance targets. These guidelines have influenced clinical practice in a significant way, and adoption of higher fill volumes has become common in North America. Several studies, however, have challenged the relevance of increasing small solute clearance; this practice may result in untoward consequences in patients. OBJECTIVE: The present study was designed to explore the relationship between dialysate volume and the clearance of different sized molecules, fluid dynamics, and appearance of peritoneal cytokines. METHODS: Thirteen adult prevalent patients on continuous ambulatory peritoneal dialysis were studied. Three different dialysate volumes (2.0, 2.5, and 3.0 L) were infused on consecutive days in a random order. Several measurements of peritoneal fluid dynamics (intraperitoneal pressure, net ultrafiltration, fluid absorption), solute clearances (urea, creatinine, beta2-microglobulin, albumin, IgG, and transferrin), and appearance of interleukin-6 and tumor necrosis factor alpha (TNFalpha) were assessed. RESULTS: Increase in dialysate fill volume (from 2 to 2.5 to 3 L) was examined in relationship to body surface area (BSA). The dialysate volume/BSA (DV/BSA) ratio increased from 1262 to 1566 to 1871 mL/m2 on 2.0, 2.5, and 3.0 L dialysate volumes, respectively. In parallel, diastolic blood pressure increased from 82.7 +/- 8.8 to 87.0 +/- 9.5 to 92 +/- 8.3 mmHg (p < 0.05). Net ultrafiltration rate also increased, from 0.46 +/- 0.48 to 0.72 +/- 0.42 to 0.97 +/- 0.49 mL/minute (p < 0.01), despite a concomitant increase in fluid absorption, from 1.05 +/- 0.34 to 1.21 +/- 0.40 to 1.56 +/- 0.22 mL/min (p < 0.01). Urea peritoneal clearance increased from 8.27 +/- 0.68 to 9.92 +/- 1.6 to 12.98 +/- 4.03 mL/min (p < 0.01); creatinine peritoneal clearance increased from 6.69 +/- 1.01 to 7.64 +/- 1.12 to 8.69 +/- 1.76 mL/min (p < 0.01). Clearance of the other measured molecules did not change. Appearance of interleukin-6 increased 17% and 43% (p < 0.01), and TNFalpha appearance increased 14% and 50% (p < 0.01) when dialysate volumes of 2.5 and 3.0 L were used, compared with 2.0 L. CONCLUSIONS: These results show that, with higher values of DV/BSA ratio, small solute peritoneal clearance is increased, but clearances of large molecules remain unchanged. With the use of higher volumes, fluid absorption rate and the appearance of proinflammatory cytokines in the dialysate are increased.     

Changes in water transport across the peritoneum during treatment with continuous ambulatory peritoneal dialysis in selected patients with and without peritonitis.

BACKGROUND: The natural course of longitudinal changes in peritoneal permeability and membrane area has been studied mostly by performing single-dwell studies in selected patients during treatment with peritoneal dialysis. PURPOSE: To evaluate the permeability characteristics of the peritoneal membrane by measuring drained ultrafiltration volume relative to initial glucose concentration in dialysis fluid from the start to the end of continuous ambulatory peritoneal dialysis (CAPD) treatment in a selected cohort of patients with and without peritonitis. DESIGN: A retrospective analysis of a group of patients whose peritoneal function was prospectively followed by recording drained ultrafiltration volume and glucose concentration in dialysis fluid for each dwell time, every day, during the time in CAPD treatment. Mean values from a 1-month period starting after the first 3 weeks of CAPD treatment were compared with the mean values from the last month of treatment. Approximately 11 500 exchanges were analyzed. Evaluations were done separately for short (day) and long (night) dwell times. PATIENTS AND STATISTICS: Of 132 patients commencing CAPD treatment in the time period selected for inclusion, 51 had enough data to be included in this study. Of these, 29 patients experienced one or more episodes of successfully treated peritonitis. The selection of patients was not based upon patient characteristics, but upon criteria to satisfy predefined demands, such as number of measurements in each period, time since an episode of peritonitis, and time on CAPD treatment. Data were analyzed in three different groups: patients with episodes of peritonitis, patients without peritonitis, and both groups together. To assess changes between monthly mean at the start and at the end of CAPD, paired t-test was performed. Patients were also stratified into two groups according to low and high glucose in dialysis fluid at the start of CAPD (cutoff = 2 g/dL). Additionally, we used linear regression analyses to predict the level of drained ultrafiltration volume for a given level and change in glucose concentration. Mean treatment time for the entire group was 20 months (median 14.3 months), ranging from 6 to 69 months. RESULTS: No statistical differences in glucose concentrations were found between the periods compared. In the entire group there was an increase in ultrafiltration volume from the start to the end of CAPD treatment, for both day (p = 0.009) and night (p = 0.013) exchanges. Also, for patients without peritonitis, an increase appeared for day (p = 0.046) and night exchanges (p = 0.053). However, for the cohort with peritonitis, only an insignificant increase was indicated. Patient characteristics, diabetic patients, the need for glucose in dialysis fluid when commencing CAPD treatment, the number of episodes of peritonitis, and time on CAPD did not influence the change in ultrafiltration. Regression analyses showed higher ultrafiltration response to a given level and change in glucose concentration at the end of CAPD treatment compared to the start values, also for the cohort with peritonitis. The regression coefficient between these variables was also significantly changed for both day (p < 0.0001) and night (p = 0.027) exchanges. CONCLUSION: A significant change in the regression coefficient between glucose in dialysis fluid and ultrafiltration volume reflects an increase in ultrafiltration response to a given level and change in glucose concentration during time on CAPD treatment. A parallel change after 5- and 9-hour dwells can be explained by a decrease in peritoneal surface area combined with a lesser decrease in peritoneal conductivity. However, changes in Starling forces across the peritoneal membrane are possible even in the absence of changes in peritoneal membrane characteristics.     

Effect of erythropoietin in continuous ambulatory peritoneal dialysis patients: comparison between intravenous and intraperitoneal administration.

The administration of recombinant human erythropoietin (rHuEPO) in CAPD patients is usually done subcutaneously. Only a few authors have reported on its intraperitoneal (IP) administration. We compared the effect of IP administration of rHuEPO in CAPD patients to that of intravenous (IV) administration. Ten anemic CAPD patients injected rHuEPO into their dialysis bag once a day, 3 times a week, for 18 weeks. The initial dose was 12,000 U. The dwell time of the exchanges with rHuEPO was about 6 hours. Nine other anemic CAPD patients were treated with IV rHuEPO once a week for 18 weeks. The initial dose was 6000 U. In the IP group the hematocrit rose from 24.04 +/- 2.7% to 33.3 +/- 3.8% (mean +/- SD). In the IV group 2 patients were excluded from the efficiency evaluation. In 7 of the 9 patients in the IV group, the hematocrit rose from 23.27 +/- 2.6% to 32 +/- 5.5% (mean +/- SD). The intraperitoneal administration of rHuEPO in CAPD patients is sufficient in improving anemia, although it requires a much larger dosage to yield the same level of improvement as the one obtained with the intravenous administration. However, in patients on continuous cycling peritoneal dialysis or IP dialysis, a smaller dosage during the prolonged dwell time may be effective.     

Intraperitoneal administration of recombinant human erythropoietin.

OBJECTIVE: To determine the efficacy and safety of intraperitoneal administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients compared to subcutaneous rHuEPO. DESIGN: Prospective analysis of an open, nonrandomized investigation. SETTING: Outpatient CAPD clinics in two university hospitals. PATIENTS: Nine adult CAPD patients receiving rHuEPO intraperitoneally and 8 patients receiving rHuEPO subcutaneously. INTERVENTION: One hundred units of rHuEPO per kilogram of body weight were administered three times a week for 8 weeks or until the target hematocrit of 35% was reached. Thereafter, dosages of rHuEPO were adjusted for response. Intraperitoneal rHuEPO was administered in 1 L of dialysis solution during the night. MEASUREMENTS: Efficacy was assessed by measuring the increase in hemoglobin. Tolerance was assessed by monitoring side effects. RESULTS: In the first 8 weeks of treatment hemoglobin concentration increased from 64.5 +/- 12.9 g/L to 98.3 +/- 16.1 g/L (p < 0.0005) in the intraperitoneally treated group. In the subcutaneously treated group hemoglobin increased significantly faster (p < 0.05) from 72.5 +/- 4.8 g/L to 119.2 +/- 11.3 g/L (p < 0.0005) in the same period. Antihypertensive medication had to be increased or instituted in most of the patients in both groups. The incidence of peritonitis in the intraperitoneally treated group was not increased when compared to the pretreatment incidence. CONCLUSIONS: Subcutaneously administered rHuEPO is superior to intraperitoneally administered rHuEPO with regard to the required dosages. However, the results of this study show that intraperitoneal administration of rHuEPO might be a convenient and safe alternative when subcutaneous administration is undesirable.     

The effect of recombinant erythropoietin on the early hematocrit rise after CAPD initiation.

OBJECTIVE: To determine if the simultaneous initiation of continuous ambulatory peritoneal dialysis (CAPD) and Erythropoietin therapy masks the hematocrit (Hct) rise that frequently follows the initiation of CAPD alone. DESIGN: Single-center retrospective analysis. SETTING: University multidisciplinary dialysis program. PATIENTS: All adult CAPD patients with a Hct less than or equal to 28% whose nephrologist felt they would benefit from Erythropoietin therapy and who did not have technical reasons for exclusion (N = 25). INTERVENTIONS: Eight patients began CAPD and Erythropoietin alfa subcutaneously, at a dose of 128 +/- 9 (X +/- SEM) units/kg/week at the same time. Seventeen patients already on CAPD for 8.7 +/- 1.5 months received Erythropoietin alfa subcutaneously at a dose of 124 +/- 7 units/kg/week. Pre-epoetin Hct's were similar. MAIN OUTCOME MEASURES: Hematocrit changes, status of iron stores, incidence of peritonitis, and dosage of Erythropoietin. RESULTS: In 1 month, the group initiating both therapies simultaneously demonstrated a mean Hct rise of 7.6 +/- 0.5% while established CAPD patients receiving Erythropoietin increased their Hct by only 4.7 +/- 1.0% (p less than .03). Iron status could not explain this difference. Peritonitis did not appear to dampen the Hct rise following Erythropoietin in either CAPD group. By 2 months after Erythropoietin, the differences were less apparent. CONCLUSION: The early rapid increase in Hct is probably the combined effect of CAPD and Erythropoietin and should not be attributed to Erythropoietin alone. When comparing responses to Erythropoietin from patients on different therapies, the timing of dialysis initiation and Erythropoietin initiation must be considered.     

Continuous ambulatory peritoneal dialysis is responsible for an increase in plasma norepinephrine.

OBJECTIVE: To investigate the reason for increasing norepinephrine (NE) levels reported in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Norepinephrine was measured in the plasma and peritoneal dialysate of CAPD patients (n = 22) and in the plasma and the urine of healthy subjects (n = 20). It was also measured in the plasma of patients with chronic renal failure (CRF) (n = 15) and patients on hemodialysis (HD) (n = 15). RESULTS: It was found that NE was increased in CAPD patients compared with healthy individuals (687+/-221 pg/mL vs 199+/-25 pg/mL, p < 0.01).The daily removal of NE from the peritoneum of CAPD patients was lower compared with the amount of NE excreted in the urine of healthy subjects. Plasma NE increased after infusion of peritoneal dialysate. In 15 new patients on CAPD, it was found that NE plasma levels increased from 329+/-67 pg/mL before initiation of dialysis, to 584+/-173 pg/mL after 12 months of treatment (p < 0.01). Finally, plasma NE in CAPD patients (687+/-221 pg/mL) was significantly higher compared with the already increased levels in patients on HD or with CRF (406+/-143 pg/mL and 378+/-142 pg/mL, respectively). CONCLUSIONS: It is concluded that CAPD in patients with end-stage renal disease is responsible for a progressive increase of plasma norepinephrine.     

Red blood cell calcium level in chronic renal failure: effect of continuous ambulatory peritoneal dialysis

Red blood cell (RBC) calcium, calcium 45 influx, and calcium extrusion as indicated by Ca-stimulated, Mg-dependent adenosine triphosphatase (CaATPase) was determined in patients with chronic renal failure (CRF), patients with CRF receiving continuous ambulatory peritoneal dialysis (CAPD) treatment, and controls. Cell calcium, which in the controls was 5.5 mumol/L of cells, was elevated in patients with CRF--30.6 +/- 6.8 mumol/L of cells (p less than 0.002)--and in patients receiving CAPD-23.6 +/- 6.7 mumol/L of cells (p less than 0.02). Basal CaATPase activity in controls was 850.7 +/- 66.7 nmol inorganic phosphate per milligram of protein per hour. It was suppressed in patients with CRF and patients receiving CAPD: 504.9 +/- 34.4 nmol inorganic phosphate per milligram of protein per hour and 618.2 +/- 47.3 nmol inorganic phosphate per milligram of protein per hour, respectively (p less than 0.01). Calmodulin-stimulated CaATPase revealed a pattern similar to that of CaATPase basal activity. RBC calcium showed an inverse correlation with CaATPase activity (r = -0.935, p less than 0.005) in patients with CRF. Calcium influx was increased in patients with CRF and in patients receiving CAPD: 12.00 +/- 1.34 mumol/L of cells per hour and 13.60 +/- 1.70, respectively, compared with 4.61 +/- 0.39 mumol/L of cells per hour in controls (p less than 0.001). Patients with CRF have elevated RBC calcium levels mainly related to decreased extrusion and to increased influx. CAPD fails to improve substantially these abnormalities. Plasma vanadium levels were markedly elevated in patients undergoing hemodialysis and marginally in patients receiving CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)